Effect of Na/Ca Exchange on Plateau Fraction and [Ca]i in Models for Bursting in Pancreatic Beta-Cells (Model C)

Effect of Na/Ca Exchange on Plateau Fraction and [Ca]i in Models for Bursting in Pancreatic Beta-Cells

Model Status

This CellML model represents Model III from the published paper. The CellML matches the published equations and the model runs in OpenCell and COR but it does not replicate the published results.

Model Structure

ABSTRACT: In the presence of an insulinotropic glucose concentration, beta-cells, in intact pancreatic islets, exhibit periodic bursting electrical activity consisting of an alternation of active and silent phases. The fraction of time spent in the active phase over a period is called the plateau fraction and is correlated with the rate of insulin release. However, the mechanisms that regulate the plateau fraction remain unclear. In this paper we investigate the possible role of the plasma membrane Na+/Ca2+ exchange of the beta-cell in controlling the plateau fraction. We have extended different single-cell models to incorporate this Ca2+-activated electrogenic Ca2+ transporter. We find that the Na+/Ca2+ exchange can provide a physiological mechanism to increase the plateau fraction as the glucose concentration is raised. In addition, we show theoretically that the Na+/Ca2+ exchanger is a key regulator of the cytoplasmic calcium concentration in clusters of heterogeneous cells with gap-junctional electrical coupling.